EPB42

Summary

EPB42 (erythrocyte membrane protein band 4.2, HGNC:3381) is a protein-coding gene on chromosome 15q15.2, encoding Protein 4.2 (P16452). Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.

Erythrocyte membrane protein band 4.2 is an ATP-binding protein which may regulate the association of protein 3 with ankyrin. It probably has a role in erythrocyte shape and mechanical property regulation. Mutations in the EPB42 gene are associated with recessive spherocytic elliptocytosis and recessively transmitted hereditary hemolytic anemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2038 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary spherocytosis type 5 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 295 total — 8 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 31
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001114134

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3381
Approved symbol	EPB42
Name	erythrocyte membrane protein band 4.2
Location	15q15.2
Locus type	gene with protein product
Status	Approved
Aliases	PA, MGC116735, MGC116737
Ensembl gene	ENSG00000166947
Ensembl biotype	protein_coding
OMIM	177070
Entrez	2038

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000441366, ENST00000540029, ENST00000565459, ENST00000567019, ENST00000569204, ENST00000648595

RefSeq mRNA: 2 — MANE Select: NM_001114134 NM_000119, NM_001114134

CCDS: CCDS10093, CCDS45249

Canonical transcript exons

ENST00000441366 — 13 exons

Exon	Start	End
ENSE00001108062	43211416	43211534
ENSE00001108063	43216268	43216453
ENSE00001108079	43215095	43215328
ENSE00001108082	43210335	43210439
ENSE00001108085	43209274	43209451
ENSE00001527058	43220816	43221018
ENSE00002614597	43197227	43197464
ENSE00003490180	43208230	43208333
ENSE00003525733	43203115	43203275
ENSE00003527135	43201844	43201977
ENSE00003610597	43208637	43208775
ENSE00003628763	43207199	43207441
ENSE00003656907	43206330	43206629

Expression profiles

Bgee: expression breadth broad, 91 present calls, max score 91.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8420 / max 970.5454, expressed in 70 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149592	1.5631	57
149589	0.1002	15
149591	0.1000	10
149588	0.0511	13
149590	0.0276	5

Top tissues by expression

123 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	91.91	gold quality
bone marrow	UBERON:0002371	91.54	gold quality
bone marrow cell	CL:0002092	88.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.87	gold quality
monocyte	CL:0000576	82.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.31	gold quality
thymus	UBERON:0002370	79.43	silver quality
leukocyte	CL:0000738	78.66	gold quality
quadriceps femoris	UBERON:0001377	74.95	gold quality
placenta	UBERON:0001987	68.68	gold quality
adrenal tissue	UBERON:0018303	64.76	gold quality
cerebellar vermis	UBERON:0004720	63.05	gold quality
right testis	UBERON:0004534	62.99	gold quality
testis	UBERON:0000473	61.35	gold quality
omental fat pad	UBERON:0010414	61.33	gold quality
adipose tissue	UBERON:0001013	61.15	gold quality
left testis	UBERON:0004533	61.02	gold quality
subcutaneous adipose tissue	UBERON:0002190	60.56	gold quality
ganglionic eminence	UBERON:0004023	60.33	gold quality
gall bladder	UBERON:0002110	56.05	gold quality
spleen	UBERON:0002106	55.90	gold quality
ventricular zone	UBERON:0003053	52.83	gold quality
thoracic mammary gland	UBERON:0005200	46.95	gold quality
right lung	UBERON:0002167	46.34	gold quality
right lobe of liver	UBERON:0001114	43.88	gold quality
colonic epithelium	UBERON:0000397	43.85	silver quality
cortical plate	UBERON:0005343	43.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	42.61	gold quality
lung	UBERON:0002048	42.54	gold quality
right atrium auricular region	UBERON:0006631	41.86	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	556.25
E-CURD-112	yes	62.07
E-MTAB-10042	yes	49.51
E-MTAB-9221	yes	18.98
E-MTAB-9067	yes	9.97
E-HCAD-9	yes	8.85
E-HCAD-10	yes	5.56
E-MTAB-9467	no	2.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CBFA2T3, GATA1, MYC, SMARCA1, TAL1

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 7)

• spectrin binding domain (PMID:12049649)
• Evidence protein 4.2 interacts with the Rh membrane complex member CD47 obtained from red cells of patients with hereditary spherocytosis associated with complete protein 4.2 deficiency (PMID:12393467)
• protein 4.2 strongly influences CD47 levels as well as the extent of membrane skeleton attachment in erythrocytes (PMID:14551146)
• The interactions of three protein 4.2-derived recombinant proteins with CDB3 and ankyrin were investigated by using Far-Western blot and pull-down assay. (PMID:16718373)
• Current understanding of protein 4.2, its known interactions & implications of protein 4.2 deficiency are reviewed. A new speculative “open” homology structure for the the active, membrane associated form is proposed. Review. (PMID:19269200)
• Data suggest that one or both of proteins 4.1 and 4.2 cause a portion of band 3 to localize near the spectrin-actin junctions and provide another point of attachment between the membrane skeleton and the lipid bilayer. (PMID:20007969)
• study shows that cytoplasmic hereditary spherocytosis mutants cause impaired binding of protein 4.2 to AE1, leaving protein 4.2 susceptible to loss during erythrocyte development (PMID:21039340)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tgm8	ENSDARG00000097651
danio_rerio	tgm5l	ENSDARG00000098837
mus_musculus	Epb42	ENSMUSG00000023216
rattus_norvegicus	Epb42	ENSRNOG00000011649

Paralogs (8): TGM1 (ENSG00000092295), TGM5 (ENSG00000104055), F13A1 (ENSG00000124491), TGM3 (ENSG00000125780), TGM7 (ENSG00000159495), TGM4 (ENSG00000163810), TGM6 (ENSG00000166948), TGM2 (ENSG00000198959)

Protein

Protein identifiers

Protein 4.2 — P16452 (reviewed: P16452)

Alternative names: Erythrocyte membrane protein band 4.2

All UniProt accessions (4): P16452, F5H563, H3BPV8, H3BUR1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.

Subunit / interactions. Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts with SLC4A1 (via the cytoplasmic domain); this interaction is mediated by the SLC4A1 Band 3-I dimer. Interacts with ANK1 (via ANK 1-13 repeats). Interacts with AQP1 (via the C-terminal).

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton.

Post-translational modifications. Both cAMP-dependent kinase (CAPK) and another kinase present in the red-blood cells seem to be able to phosphorylate EPB42.

Disease relevance. Spherocytosis 5 (SPH5) [MIM:612690] Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Absence of band 4.2 associated with spur or target erythrocytes has also been reported. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The substitution of an Ala for a Cys in the active site may be responsible for the lack of transglutaminase activity of band 4.2. Major isoform.

Similarity. Belongs to the transglutaminase superfamily. Transglutaminase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P16452-1	Short	yes
P16452-2	Long
P16452-3	3

RefSeq proteins (2): NP_000110, NP_001107606* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001102	Transglutaminase_N	Domain
IPR002931	Transglutaminase-like	Domain
IPR008958	Transglutaminase_C	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR013808	Transglutaminase_AS	Active_site
IPR014756	Ig_E-set	Homologous_superfamily
IPR023608	Transglutaminase_animal	Family
IPR036238	Transglutaminase_C_sf	Homologous_superfamily
IPR036985	Transglutaminase-like_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050779	Transglutaminase	Family

Pfam: PF00868, PF00927, PF01841

Enzyme classification (BRENDA):

• EC 2.3.2.13 — protein-glutamine gamma-glutamyltransferase (BRENDA: 68 organisms, 476 substrates, 772 inhibitors, 122 Km, 49 kcat entries)

Substrate kinetics (BRENDA)

60 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PUTRESCINE	0.035–9.63	13
L-LYSINE	2.9–15.8	6
N-CBZ-GLN-GLY	12.83–59.5	5
HYDROXYLAMINE	1.37–61.9	4
NALPHA-BENZYLOXYCARBONYL-L-GLN-GLY	11.2–30	4
CASEIN	0.006–0.012	3
CBZ-GLN-GLY	0.0169–5.9	3
CBZ-GLN-GLY-OH	3.53–8.55	3
METHYLAMINE	0.024–0.061	3
MONODANSYLCADAVERINE	0.01–0.034	3
N-CARBOXYBENZOYL-L-GLUTAMINYL-GLYCINE	0.0547–69.4	3
PENTYLAMINE	0.0029–0.0203	3
Z-GLN-GLY	1.8–11.6	3
ACETYL-ALPHAS1-CASEIN	0.0029–0.0032	2
GTP	0.0044–0.01	2

UniProt features (70 total): strand 40, helix 14, sequence variant 4, turn 3, sequence conflict 2, splice variant 2, initiator methionine 1, chain 1, region of interest 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
7UZS	ELECTRON MICROSCOPY	2.2
7V0K	ELECTRON MICROSCOPY	2.4
7V0Q	ELECTRON MICROSCOPY	2.5
8CSW	ELECTRON MICROSCOPY	2.5
8CS9	ELECTRON MICROSCOPY	2.74
8CTE	ELECTRON MICROSCOPY	2.9
7TVZ	ELECTRON MICROSCOPY	3.6
7TW3	ELECTRON MICROSCOPY	4.4
7TW0	ELECTRON MICROSCOPY	4.6
7TW1	ELECTRON MICROSCOPY	4.6
7TW6	ELECTRON MICROSCOPY	5.6
7TW5	ELECTRON MICROSCOPY	5.7
8CSL	ELECTRON MICROSCOPY	25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16452-F1	89.35	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 248, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 198 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_HEMOGLOBIN_METABOLIC_PROCESS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_PEPTIDE_CROSS_LINKING, GOBP_ERYTHROCYTE_HOMEOSTASIS, GNF2_ANK1, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_ANATOMICAL_STRUCTURE_MATURATION, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GATA3_01, GOBP_CELL_MATURATION, MODULE_206

GO Biological Process (9): cell morphogenesis (GO:0000902), regulation of cell shape (GO:0008360), hemoglobin metabolic process (GO:0020027), erythrocyte maturation (GO:0043249), spleen development (GO:0048536), multicellular organismal-level iron ion homeostasis (GO:0060586), cytoskeleton organization (GO:0007010), peptide cross-linking (GO:0018149), monoatomic ion homeostasis (GO:0050801)

GO Molecular Function (4): protein-glutamine gamma-glutamyltransferase activity (GO:0003810), structural constituent of cytoskeleton (GO:0005200), ATP binding (GO:0005524), protein binding (GO:0005515)

GO Cellular Component (7): cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cortical cytoskeleton (GO:0030863), ankyrin-1 complex (GO:0170014), cytoplasm (GO:0005737), membrane (GO:0016020), cell periphery (GO:0071944)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoskeleton	2
anatomical structure morphogenesis	1
regulation of cell morphogenesis	1
regulation of biological quality	1
protein metabolic process	1
cell maturation	1
erythrocyte development	1
hematopoietic or lymphoid organ development	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
multicellular organismal-level chemical homeostasis	1
organelle organization	1
protein modification process	1
chemical homeostasis	1
aminoacyltransferase activity	1
catalytic activity, acting on a protein	1
structural molecule activity	1
cytoskeleton organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
binding	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
cell cortex	1
membrane protein complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPB42	SLC4A1	P02730	893
EPB42	SPTA1	P02549	773
EPB42	ANK1	P16157	766
EPB42	CDAN1	Q8IWY9	741
EPB42	FECH	P22830	719
EPB42	EPB41	P11171	717
EPB42	TAL1	P17542	683
EPB42	DMTN	Q08495	670
EPB42	RHAG	Q02094	664
EPB42	ALAS2	P22557	612
EPB42	ADD2	P35612	576
EPB42	AHSP	Q9NZD4	570
EPB42	BLOC1S6	Q9UL45	561
EPB42	TMOD1	P28289	559
EPB42	TAL2	Q16559	549

IntAct

12 interactions, top by confidence:

A	B	Type	Score
KLK6	EPB42	psi-mi:“MI:0915”(physical association)	0.560
SPINK7	EPB42	psi-mi:“MI:0915”(physical association)	0.550
EPB42	SPINK7	psi-mi:“MI:0915”(physical association)	0.550
SLC4A1	FLOT1	psi-mi:“MI:0914”(association)	0.530
EPB42	ZNF16	psi-mi:“MI:0915”(physical association)	0.370
AQP1	FLOT1	psi-mi:“MI:0914”(association)	0.350
EPB42	HSPA8	psi-mi:“MI:0914”(association)	0.350
EPB42	MAPK14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): SLC4A7 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), SNX6 (Affinity Capture-MS), EPB42 (Affinity Capture-MS), EPB42 (Two-hybrid), EPB42 (Two-hybrid), ANK2 (Reconstituted Complex), SLC4A1 (Protein-peptide), EPB42 (Reconstituted Complex), SLC4A7 (Affinity Capture-MS), SNX6 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), EPB42 (Reconstituted Complex), EPB42 (Affinity Capture-RNA), EPB42 (Two-hybrid)

ESM2 similar proteins: A0A8C2MDK8, A0A8I6GM68, A6H751, A7YY46, A8MX76, D3YXS5, D3ZBP4, D3ZEY4, E7F9T0, E9QAM5, F1MH07, F1QCV2, F8WLE0, P16452, P23249, P48760, P49222, P52824, Q2NKY8, Q2QWU2, Q3SYT1, Q3ZBE0, Q4R380, Q50L43, Q5BJS0, Q5NCQ5, Q5R607, Q5RKI3, Q5ZI74, Q69ZP3, Q6P5E8, Q6ZSI9, Q7L2E3, Q8BX80, Q8N490, Q8NFD2, Q8NFI3, Q8TDZ2, Q8TE96, Q8VDP3

Diamond homologs: A6QP57, D4A5U3, O08619, O43548, O46510, O95932, P00488, P08587, P16452, P21980, P21981, P22735, P22758, P23606, P49221, P51176, P52181, P52183, Q01841, Q05187, Q08188, Q08189, Q8BH61, Q8BZH1, Q96PF1, Q99041, Q9D7I9, Q9GLK0, Q9JLF6, Q9WVJ6, P49222, P12260

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EPB42	“form complex”	“Ankyrin complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

295 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	10
Uncertain significance	163
Likely benign	52
Benign	21

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
13234	NM_001114134.2(EPB42):c.175del (p.Val59fs)	Pathogenic
13236	NM_000119.2(EPB42):c.922+1G>A	Pathogenic
13237	NM_000119.2(EPB42):c.1747G>T (p.Glu583Ter)	Pathogenic
132633	NM_001114134.2(EPB42):c.433G>T (p.Asp145Tyr)	Pathogenic
1912307	NM_001114134.2(EPB42):c.1660C>T (p.Arg554Ter)	Pathogenic
2130840	NM_001114134.2(EPB42):c.1641_1648del (p.Phe548fs)	Pathogenic
4078703	NM_001114134.2(EPB42):c.1423_1454del (p.Leu475fs)	Pathogenic
4685821	NM_001114134.2(EPB42):c.1305C>G (p.Tyr435Ter)	Pathogenic
1163094	NM_001114134.2(EPB42):c.293_300dup (p.Ser101fs)	Likely pathogenic
1163381	NM_001114134.2(EPB42):c.619_628del (p.Gln207fs)	Likely pathogenic
13235	NM_000119.2(EPB42):c.929G>A (p.Arg310Gln)	Likely pathogenic
1324335	NM_001114134.2(EPB42):c.1501del (p.Ser501fs)	Likely pathogenic
2921044	NM_001114134.2(EPB42):c.1887del (p.Leu630fs)	Likely pathogenic
3577129	NM_001114134.2(EPB42):c.108dup (p.Gln37fs)	Likely pathogenic
4081372	NM_001114134.2(EPB42):c.1686del (p.Arg563fs)	Likely pathogenic
4081373	NM_001114134.2(EPB42):c.1350_1351del (p.Arg450fs)	Likely pathogenic
992935	NM_001114134.2(EPB42):c.832G>C (p.Val278Leu)	Likely pathogenic
992936	NM_001114134.2(EPB42):c.323C>T (p.Thr108Ile)	Likely pathogenic

SpliceAI

2207 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43201838:ACTT:A	donor_loss	1.0000
15:43201839:CTTA:C	donor_loss	1.0000
15:43201840:TTACC:T	donor_loss	1.0000
15:43201841:TACCT:T	donor_loss	1.0000
15:43201843:C:CT	donor_loss	1.0000
15:43203109:GCCTA:G	donor_loss	1.0000
15:43203110:CCTA:C	donor_loss	1.0000
15:43203111:CTACC:C	donor_loss	1.0000
15:43203112:TAC:T	donor_loss	1.0000
15:43203113:ACCT:A	donor_loss	1.0000
15:43203114:CCT:C	donor_loss	1.0000
15:43203152:T:TA	donor_gain	1.0000
15:43203276:C:CC	acceptor_gain	1.0000
15:43206363:T:TA	donor_gain	1.0000
15:43206628:CC:C	acceptor_gain	1.0000
15:43206629:CC:C	acceptor_gain	1.0000
15:43206629:CCT:C	acceptor_loss	1.0000
15:43206630:C:CC	acceptor_gain	1.0000
15:43206630:C:T	acceptor_gain	1.0000
15:43207195:GTA:G	donor_loss	1.0000
15:43207437:CAGGA:C	acceptor_gain	1.0000
15:43207438:AGGA:A	acceptor_gain	1.0000
15:43207442:C:CC	acceptor_gain	1.0000
15:43208776:C:CC	acceptor_gain	1.0000
15:43209272:ACCTG:A	donor_loss	1.0000
15:43209301:AGG:A	donor_gain	1.0000
15:43209447:TGCAG:T	acceptor_gain	1.0000
15:43209448:GCAG:G	acceptor_gain	1.0000
15:43209449:CAGC:C	acceptor_gain	1.0000
15:43220739:T:TA	donor_gain	1.0000

AlphaMissense

4496 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:43209362:G:C	S248R	0.985
15:43209362:G:T	S248R	0.985
15:43209364:T:G	S248R	0.985
15:43208732:A:C	F292L	0.964
15:43208732:A:T	F292L	0.964
15:43208734:A:G	F292L	0.964
15:43208269:A:G	W346R	0.961
15:43208269:A:T	W346R	0.961
15:43211430:A:G	W179R	0.961
15:43211430:A:T	W179R	0.961
15:43208748:C:G	R287P	0.958
15:43209278:G:C	C276W	0.951
15:43208267:C:A	W346C	0.950
15:43208267:C:G	W346C	0.950
15:43211428:C:A	W179C	0.948
15:43211428:C:G	W179C	0.948
15:43207209:C:A	K436N	0.947
15:43207209:C:G	K436N	0.947
15:43207359:A:C	F386L	0.947
15:43207359:A:T	F386L	0.947
15:43207361:A:G	F386L	0.947
15:43208739:G:A	T290I	0.947
15:43208311:A:G	C332R	0.945
15:43203198:C:G	A566P	0.938
15:43208327:G:C	F326L	0.937
15:43208327:G:T	F326L	0.937
15:43208329:A:G	F326L	0.937
15:43208749:G:T	R287S	0.936
15:43215108:G:C	N139K	0.936
15:43215108:G:T	N139K	0.936

dbSNP variants (sampled 300 via entrez): RS1000000558 (15:43202684 G>A), RS1000040721 (15:43212382 A>G), RS1000215593 (15:43213366 C>T), RS1000233807 (15:43223435 A>G), RS1000242407 (15:43204687 T>C), RS1000296524 (15:43217041 G>A), RS1000515431 (15:43207025 A>G), RS1000575422 (15:43208490 T>C), RS1000607436 (15:43213837 A>G), RS1000651321 (15:43214045 G>C), RS1000816259 (15:43211891 C>T), RS1000908909 (15:43226896 G>A), RS1000913011 (15:43212068 TA>T,TAA), RS1001180584 (15:43209988 C>A,T), RS1001294459 (15:43215492 G>A)

Disease associations

OMIM: gene MIM:177070 | disease phenotypes: MIM:612690

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spherocytosis type 5	Strong	Autosomal recessive
hereditary spherocytosis	Supportive	Autosomal dominant

Mondo (2): hereditary spherocytosis type 5 (MONDO:0012985), hereditary spherocytosis (MONDO:0019350)

Orphanet (1): Hereditary spherocytosis (Orphanet:822)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000952	Jaundice
HP:0000980	Pallor
HP:0001081	Cholelithiasis
HP:0001251	Ataxia
HP:0001324	Muscle weakness
HP:0001510	Growth delay
HP:0001723	Restrictive cardiomyopathy
HP:0001744	Splenomegaly
HP:0001878	Hemolytic anemia
HP:0001903	Anemia
HP:0001923	Reticulocytosis
HP:0001945	Fever
HP:0001978	Extramedullary hematopoiesis
HP:0001997	Gout
HP:0002027	Abdominal pain
HP:0002240	Hepatomegaly
HP:0002904	Hyperbilirubinemia
HP:0003270	Abdominal distention
HP:0003326	Myalgia
HP:0004444	Spherocytosis
HP:0005502	Increased red cell osmotic fragility
HP:0005525	Spontaneous hemolytic crises
HP:0011873	Abnormal platelet count
HP:0011893	Abnormal leukocyte count
HP:0011900	Hypofibrinogenemia
HP:0025143	Chills
HP:0025548	Increased mean corpuscular hemoglobin concentration
HP:0040186	Maculopapular exanthema
HP:0100724	Hypercoagulability

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010241_394	Apolipoprotein A1 levels	9.000000e-11
GCST010242_144	HDL cholesterol levels	4.000000e-12
GCST90002397_255	Mean spheric corpuscular volume	8.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D013103	Spherocytosis, Hereditary	C15.378.050.141.150.785; C16.320.070.785
C567202	Spherocytosis, Type 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
T-2 Toxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Aflatoxin B1	increases methylation	1
tert-Butylhydroperoxide	increases degradation	1

Clinical trials (associated diseases)

3 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01141621	Not specified	TERMINATED	The Dallas Hereditary Spherocytosis Cohort Study
NCT01276561	Not specified	WITHDRAWN	Single Incision Versus Standard Laparoscopic Splenectomy
NCT04451785	Not specified	COMPLETED	Hereditary Spherocytosis and Vascular Function